This invention comprises .alpha.-[(alkylamino)methyl]-.beta.-aryloxy-benzeneethanols and the pharmacologically acceptable acid addition salts thereof, which in standard pharmacological tests with animals have exhibited antiarrhythmic activity.
Heretofore an .alpha.-[(alkylamino)methyl]ethanol substituted in the .beta.-position by both a phenyl group and a phenoxy (or 1-naphthoxy) group has not been known. Recently, .alpha.-[(1-methylethylamino)methyl]-.gamma.-phenyl-(.gamma.-benzene)propa nol was reported to have antiarrhythmic activity by Murphy et al. in The Pharmacologist, 18, 114 (1976). An earlier Derwent abstract No. 16,563, of French Pat. No. 1,394,771, published Sept. 4, 1965, disclosed certain alkanolamine derivatives to be .beta.-adrenergic blockers. Among these was .alpha.-[(1-methylethylamino)methyl]-3-alkyl-(2-iodo)benzeneethanol.
A further aspect of the present invention is a process for the addition of an aryloxy group at the 3-position of a 3-phenyl-2-oxiranecarboxamide to produce an .alpha.-hydroxy-.beta.-aryloxybenzenepropanamide, said process comprising contacting an alkali metal aryloxide with said 3-phenyl-2-oxiranecarboxamide in the presence of a crown ether. The preparation and use of "crown ethers" as metal ion complexing agents is reported in Fieser and Fieser, Reagents for Organic Synthesis, Vol. V, pp. 152-5, Wiley-Interscience (1975) and Knipe, J. Chem. Ed., 53, 618 (1976). The influence of dibenzo or dicyclohexyl-[3n]-crown[n] crown ethers on the reaction of potassium phenoxide and butyl bromide to form phenylbutyl ether is reported on by Thomassen et al., in J. Acta Chem. Scand, 25, 3024 (1971).